Submitted on May 13, 2008
Revised on September 12, 2008
Accepted on October 28, 2008
Chronic Intermittent Hypoxia Impaired Heart Rate Responses to AMPA and NMDA and Induces a Loss of Glutamate Receptor Neurons in Nucleus Ambiguus of F344 Rats
Binbin Yan1, Lihua Li, Scott W Harden2, David Gozal3, Ying Lin, William B Wead4, Robert D. Wurster, and Zixi Jack Cheng2*
1 University of Central Florida
2 UCF
3 University of Louisville
4 UofL
* To whom correspondence should be addressed. E-mail: zcheng{at}mail.ucf.edu.
Chronic intermittent hypoxia (CIH), as occurs in sleep apnea, impairs baroreflex-mediated reductions in heart rate (HR) and enhances HR responses to electrical stimulation of vagal efferent. In this study, we tested the hypotheses that HR responses to activation of AMPA and NMDA receptors in the nucleus ambiguus (NA) are reduced in rats exposed to CIH and that this impairment is associated with degeneration of glutamate receptor immunoreactive NA neurons. Fischer 344 rats (3-4 months) were exposed to either room air (RA) or CIH for 35-50 days (n=18). At the end of the exposures, AMPA (4 pmol, 20 nl) and NMDA (80 pmol, 20 nl) were microinjected into the same location of the left NA (n=6), and HR and arterial blood pressure (AP) responses were measured. In addition, brainstem sections were processed for AMPA and NMDA receptor immunohistochemistry. The number of NA neurons expressing AMPA and NMDA receptors was quantified. Compared to RA, we found that following CIH: 1) the HR responses to microinjection of AMPA into the left NA were reduced (RA: -290 ± 30 vs. CIH: -227 ± 15 bpm, p<0.05); 2) the HR responses to microinjection of NMDA into the left NA were reduced (RA: -302 ± 16, vs. CIH: -238 ± 27 bpm, p<0.05); and 3) the number of NMDAR1, AMPA GluR1, and AMPA GluR2/3 immuno-reactive cells in the NA was reduced (p<0.05). These results suggest that degeneration of NA neurons expressing glutamate receptors contributes to impaired baroreflex control of HR in rats exposed to CIH.
